A novel imidazole-based azo molecule: synthesis, characterization, quantum chemical calculations, molecular docking, molecular dynamics simulations and ADMET properties

Atay, Çiğdem Karabacak; Dilek, Ömer; Tilki, Tahir; Dede, Bülent

doi:10.1007/s00894-023-05625-1

Cited by 8 publications

(5 citation statements)

References 51 publications

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“…The Mulliken atomic charges assigned to the atoms within the synthesized compounds align remarkably well with the distribution of electron‐rich and electron‐poor regions depicted in the molecular electrostatic potential (MEP) diagram of the compounds. This congruence highlights the correspondence between the calculated atomic charges and the expected electron density patterns within the molecular framework [34] …”

Section: Resultssupporting

confidence: 63%

“…The frontier molecular orbitals, namely the Highest Occupied Molecular Orbital (HOMO) and the Lowest Unoccupied Molecular Orbital (LUMO), play a crucial role in determining the ionization potential and electron affinity of molecules. Furthermore, the energy difference between these orbitals, referred to as the HOMO‐LUMO gap, serves as a valuable indicator for estimating various molecular properties, including stability, reactivity, conductivity, and color [34] …”

Section: Resultsmentioning

confidence: 99%

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Exploring the Potential of Azo Compounds in Leukemia Treatment: Synthesis and Characterization of New Derivatives with Dimedone and Meldrum's Acid End Groups

Güney,

Dilek,

Sezgin

et al. 2023

ChemistrySelect

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This scholarly investigation presents pioneering drug candidates for combating leukemia, distinguished by reduced side effects and elevated efficacy. The study focuses on azo compounds for their selective targeting against cancerous cells, and customizable properties. Novel azo compounds, DMTPC and DMTPD, were skillfully synthesized via diazotization of 3‐(4‐Methyl‐1H‐imidazol‐1‐yl)‐5‐(trifluoromethyl)aniline with dimedone and meldrum‘s acid. Comprehensive characterization employed advanced analytical techniques like 1H‐NMR, 13C‐NMR, LC‐MS, FT‐IR, and XRD. UV‐Vis and fluorescence spectrophotometers scrutinized absorption and fluorescence properties in diverse solvents. Theoretical DFT computations provided optimized geometries, vibrational frequencies, NMR chemical shifts, absorption wavelengths, HOMOs‐LUMOs, Mulliken charges, and molecular orbital energies. Encouragingly, experimental and theoretical values aligned well. ADME properties and toxicity profiles were evaluated using online web servers. Molecular dynamics simulations explored interactions of DMTPC and DMTPD with the leukemia inhibitory factor protein (PDB ID: 1EMR) compared to Nilotinib. Molecular docking studies indicated DMTPC′s promising potential with a binding energy of −8.8 kcal/mol, approaching Nilotinib's −9.4 kcal/mol. This investigation accentuates the burgeoning research paradigm of exploiting azo compounds in the formidable battle against leukemia, opening new avenues for breakthroughs in this field.

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Section: Resultssupporting

confidence: 63%

Section: Resultsmentioning

confidence: 99%

Exploring the Potential of Azo Compounds in Leukemia Treatment: Synthesis and Characterization of New Derivatives with Dimedone and Meldrum's Acid End Groups

Güney,

Dilek,

Sezgin

et al. 2023

ChemistrySelect

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“…Inhibition of structures such as EGFR, VEGFR2, FGFR1, and HSP90 stand out with some of these methods. There are many studies in the literature investigating the activities of these targets by modulating/inhibiting them to determine the anticancer activity. ,− In addition to anticancer activity, the compounds were examined for their potential to inhibit hCA I and hCA II enzymes. The investigation aimed to determine whether these compounds can interact with these targets and, if so, to explore the extent and manner of such interactions.…”

Section: Results and Discussionmentioning

confidence: 99%

Imidazole-Derived Alkyl and Aryl Ethers: Synthesis, Characterization, In Vitro Anticancer and Antioxidant Activities, Carbonic Anhydrase I–II Inhibition Properties, and In Silico Studies

Faris,

Bostancı,

Özcan

et al. 2024

ACS Omega

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Imidazole derivatives display extensive applications in pharmaceutical chemistry and have been investigated as bioactive compounds for medicinal chemistry. In this study, besides the starting materials (3a−c and 4a−c), synthesis, characterization, and biological activity studies were conducted on a total of 18 compounds, nine of which are known and the other nine are original. The compounds investigated in the study are a series of alkyl (7−15) and aryl (16−24) ether derivatives bearing substituted phenyl and imidazole rings, which were characterized using various methods including 1 H NMR, 13 C NMR, FT-IR analysis, elemental analysis, and mass spectroscopy. Computeraided drug design studies have been carried out to predict the biological activities of compounds. Besides DFT calculations, the binding affinities of the compounds to EGFR, VEGFR2, FGFR1, HSP90, hCA I, and hCA II were investigated. Additionally, druglikeness and ADME analyses were performed on the compounds. Anticancer, antioxidant, and enzyme inhibition activity tests were performed in biological activity studies on the synthesized compounds. Among the synthesized compounds, compounds 17 and 19− 24 generally exhibited inhibition profiles against the widespread cytosolic hCA I isozyme with IC 50 values ranging from 4.13 to 15.67 nM and cytosolic hCA II isozyme with IC 50 values ranging from 5.65 to 14.84 nM. L929 (mouse fibroblast cell line) was used as the control healthy cell line, and MCF7 (breast cancer), C6 (rat glioblastoma), and HT-29 (colon cancer) cells were used in cell culture studies as cancer cell lines. Before the study on cancer cells, all compounds were examined on healthy cells, and their cytotoxicity was determined. As a result of these data, studies continued with six compounds determined to be nontoxic. On cancerous cells, it was determined that compounds 3a, 3b, 4a, 4b, 4c, and 7 had cytotoxic effects on both colon cancer and brain tumors. It was found that compound 3b had a more toxic effect than cisplatin on the glioma cell line with an IC 50 value of 10.721 ± 0.38 μM, and compound 3a had a more toxic effect on the colon cancer cell line with an IC 50 value of 20.88 ± 1.02 μM. However, it was determined that the same compounds did not have a statistically significant effect on breast cancer. Flow cytometry studies also showed that when the IC 50 dose of compound 3b was applied to the C6 cell line, the cells tended to early and late apoptosis. Additionally, it has been shown by flow cytometry that the cell cycle stops in the G0/G1 phase. A similar effect was observed in the colon cancer cell line with compound 3a. Compound 3b caused early and late apoptosis of the colon cancer cell line with the applied IC 50 dose and stopped the cell cycle in the G0/G1 phase. Finally, the FRAP method studied all synthesized compounds' antioxidant effects. According to the measured antioxidant power results, it was determined that no compound had a more effective reducing power than vitamin E.

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“…Active sites of 2XIR and 5TGZ were surrounded by a grid box 45 x 45 x 45 Å 3 using UCSF Chimera 1.17.2. The x, y, and z coordinates of the proteins' binding sites were taken from the literature [23,24]. Avogadro software and UFF parameters [25] were used to calculate optimized geometries of compounds.…”

Section: Molecular Docking Studiesmentioning

confidence: 99%

“…By using 2XIR and 5TGZ proteins molecular docking studies of compounds (a-l) were investigated. The 3D binding site coordinates of 2XIR and 5TGZ were taken from the literature [23,24]. The all synthesized compounds were individually docked selected regions of both 2XIR and 5TGZ proteins.…”

Section: Molecular Docking Studiesmentioning

confidence: 99%

Indole-Bearing Azo Compounds: Molecular Docking and in silico ADMET Analysis

Dilek,

Tilki,

Karabacak Atay

2024

Hacettepe Journal of Biology and Chemistry

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In this study, the interaction between the 12 indole-bearing azo compounds (a-l), which were previously synthesized by our research group, and two proteins, 2XIR and 5TGZ, was investigated using an in silico method. The ligand-protein interaction parameters and quantities were determined via molecular docking simulation studies. Since compound e has the lowest docking scores for both 2XIR and 5TGZ, it was selected for additional research on binding interactions. Both e-2XIR and e-5TGZ had docking scores that were lower than those of the control molecules. ADMET characteristics (absorption, distribution, metabolism, excretion, and toxicity) were anticipated using the ADMETlab 2.0 and ProTox-II server. Compound b was categorized as having the greatest levels of toxicity, falling into the sixth toxicity class.

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A novel imidazole-based azo molecule: synthesis, characterization, quantum chemical calculations, molecular docking, molecular dynamics simulations and ADMET properties

Cited by 8 publications

References 51 publications

Exploring the Potential of Azo Compounds in Leukemia Treatment: Synthesis and Characterization of New Derivatives with Dimedone and Meldrum's Acid End Groups

Exploring the Potential of Azo Compounds in Leukemia Treatment: Synthesis and Characterization of New Derivatives with Dimedone and Meldrum's Acid End Groups

Imidazole-Derived Alkyl and Aryl Ethers: Synthesis, Characterization, In Vitro Anticancer and Antioxidant Activities, Carbonic Anhydrase I–II Inhibition Properties, and In Silico Studies

Indole-Bearing Azo Compounds: Molecular Docking and in silico ADMET Analysis

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